This invention relates to a series of penicillins and in particular to 6-[2-aryl-2-(amidino- and imodoylaminoalkanoylamino)acetamido]penicillanic acids and to the pharmaceutically acceptable salts thereof, possessing high antibacterial activity, espcially against gram-negative micro-organisms.
The compounds in the group belonging to the family of penicillins differ from each other in the nature of the R variable and possess the general formula indicated below wherein the acyl moiety on the 6-aminopenicillanic acid ##SPC1##
Is derived from a carboxylic acid or functional derivative thereof such as an acyl halide or anhydride.
The pharmacodynamic properties and antibiotic profile of a given penicillin are determined to a large extent by the nature of the R group. The most widely used penicillins are those wherein the R moiety is represented by benzyl-, phenoxymethyl- or .alpha.-phenoxyethyl-. While these well-known analogs are highly antagonistic toward gram-positive micro-organisms they have limited gram-negative activity. Consequently, drugs which will combat a rise in gram-negative infections, e.g., E. coli, Pseudomonas or Klebsiella, are of value to the medical profession.
Recent efforts to improve the profile of activity within the family of penicillins has resulted in the synthesis of several new agents. .alpha. -Carboxybenzylpenicillin (U.S. Pat. No. 3,142,673), a broad spectrum antibiotic, is reported to have greater efficacy against gram-negative bacteria via the parenteral route of administration, but has limited utility via oral administration. .alpha.-Aminoarylmethylpenicillins and congeners thereof (U.S. Pat. Nos. 2,985,648; 3,140,282; 3,373,156; 3,308,023 and 3,342,677) are known, but have a limited spectrum of activity against certain gram-negative miro-organisms. Both gram-negative and gram-positive activity are claimed for 6-ureidopenicillanic acid derivatives in U.S. Pat. Nos. 3,180,863; 3,120,512 and 3,118,877 and for .alpha.-ureidopenicillins in U.S. Pat. No. 3,352,851. Activity against gram-negative bacteria, especially those of the genus Pseudomonas, is claimed for .alpha.-carbamylureidopenicillins (U.S. Pat. No. 3,483,118) and .alpha.-alkoxycarbonylureidopenicillins (U.S. Pat. No. 3,481,922). More recently, .alpha.-guanylureidopenicillins (U.S. Pat. No. 3,579,501) and .alpha.-imidoylureidopenicillins (U.S. Pat. No. 3,634,405) have been reported to be useful against infectious diseases, especially those caused by the Pseudomonas genus.